title: Autophagy as a neuroprotective mechanism against 3-nitropropionic acid-induced murine astrocyte cell death.
abstract: Huntington's disease (HD) is a genetic neurodegenerative disorder that is characterized by severe striatal atrophy with extensive neuronal loss and gliosis. Although the molecular mechanism is not well understood, experimental studies use the irreversible mitochondrial inhibitor 3-nitropropionic acid (3-NP) to mimic the neuropathological features of HD. In this study, the role of autophagy as a neuroprotective mechanism against 3-NP-induced astrocyte cytotoxicity was evaluated. Autophagy is a catabolic process that is essential for the turnover of cytosolic proteins and organelles and is involved in the modulation of cell death and survival. We showed that 3-NP-induced apoptosis, which was accompanied by Bax and Beclin-1 upregulation, was dependent on acidic vesicular organelle (AVO) formation after a continuous exposure to 3-NP for 12 h. The upregulation of Bax and Beclin-1 as well as AVO formation were normalized 24 h after 3-NP exposure.
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), Rua Três de Maio 100, São Paulo, SP, 04044-020, Brazil.
authors.forename: Gustavo J S
authors.initials: GJ
authors.lastname: Pereira
authors.forename: Nicole
authors.initials: N
authors.lastname: Tressoldi
authors.forename: Hanako
authors.initials: H
authors.lastname: Hirata
authors.forename: Claudia
authors.initials: C
authors.lastname: Bincoletto
authors.forename: Soraya S
authors.initials: SS
authors.lastname: Smaili
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001253:Astrocytes / Q000473:pathology*; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000503:physiopathology; D051379:Mice; D009574:Nitro Compounds / Q000633:toxicity*; D011422:Propionates / Q000633:toxicity*; D020123:Sirolimus; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D009574:Nitro Compounds; D011422:Propionates; D051028:bcl-2-Associated X Protein; C025946:3-methyladenine; D000225:Adenine; C015392:3-nitropropionic acid; D020123:Sirolimus